Impact of long-term exposure to sodium arsenite on cytogenetic radiation damage

TY - JOUR

T1 - Impact of long-term exposure to sodium arsenite on cytogenetic radiation damage

AU - Nuta, Otilia

AU - Moquet, Jayne

AU - Bouffler, Simon

AU - Lloyd, David

AU - Sepai, Ovnair

AU - Rothkamm, Kai

PY - 2014/3

Y1 - 2014/3

N2 - The aim of this work was to investigate the impact of long-term exposure to low concentrations of sodium arsenite on the cellular response to ionising radiation. Human lymphoblastoid GM1899a cells were cultured in the presence of sodium arsenite for up to six months. Following chemical exposure, acute challenge doses of X-rays were given and chromosome damage (dicentrics, acentric fragments, translocations, micronuclei) as well as cell growth and changes in cell cycle kinetics were determined. Initial short-term chemical exposures determined 8 ng/ml (60 nM) sodium arsenite as a suitable concentration for chronic exposures, which is below the current World Health Organization limit for arsenic in drinking water. At this concentration, cell growth was slightly, but consistently, slower than in untreated cultures throughout the six-month exposure period. Long-term exposure to the chemical induced no dicentrics and did not significantly alter the yield of dicentrics induced by 1 Gy acute X-irradiation. Similar results were obtained for chromosome translocations. In contrast, exposure to 8 ng/ml sodium arsenite induced significant levels of acentric fragments and micronuclei. Fragment/micronuclei data in combined treatment samples compared with single treatments were consistent with an additive effect of chemical and radiation exposure. As for X-rays, micronuclei induced by sodium arsenite tended to show no centromere in situ hybridisation signal, indicating that they represent structural aberrations rather than mis-segregated chromosomes. Similar results were obtained in human peripheral lymphocytes following short-term exposure to sodium arsenite or X-rays. Overall, an additive effect was observed for all combined exposures. Cellular radiation responses therefore seem to operate without any modulatory effects from chronic low level exposure to sodium arsenite in the systems analysed here.

AB - The aim of this work was to investigate the impact of long-term exposure to low concentrations of sodium arsenite on the cellular response to ionising radiation. Human lymphoblastoid GM1899a cells were cultured in the presence of sodium arsenite for up to six months. Following chemical exposure, acute challenge doses of X-rays were given and chromosome damage (dicentrics, acentric fragments, translocations, micronuclei) as well as cell growth and changes in cell cycle kinetics were determined. Initial short-term chemical exposures determined 8 ng/ml (60 nM) sodium arsenite as a suitable concentration for chronic exposures, which is below the current World Health Organization limit for arsenic in drinking water. At this concentration, cell growth was slightly, but consistently, slower than in untreated cultures throughout the six-month exposure period. Long-term exposure to the chemical induced no dicentrics and did not significantly alter the yield of dicentrics induced by 1 Gy acute X-irradiation. Similar results were obtained for chromosome translocations. In contrast, exposure to 8 ng/ml sodium arsenite induced significant levels of acentric fragments and micronuclei. Fragment/micronuclei data in combined treatment samples compared with single treatments were consistent with an additive effect of chemical and radiation exposure. As for X-rays, micronuclei induced by sodium arsenite tended to show no centromere in situ hybridisation signal, indicating that they represent structural aberrations rather than mis-segregated chromosomes. Similar results were obtained in human peripheral lymphocytes following short-term exposure to sodium arsenite or X-rays. Overall, an additive effect was observed for all combined exposures. Cellular radiation responses therefore seem to operate without any modulatory effects from chronic low level exposure to sodium arsenite in the systems analysed here.

KW - Arsenites/toxicity

KW - Cell Cycle/drug effects

KW - Cell Line, Tumor

KW - Chromosome Aberrations/drug effects

KW - Flow Cytometry

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Linear Models

KW - Micronuclei, Chromosome-Defective/drug effects

KW - Sodium Compounds/toxicity

U2 - 10.1093/mutage/get070

DO - 10.1093/mutage/get070

M3 - SCORING: Journal article

C2 - 24452505

VL - 29

SP - 123

EP - 129

JO - MUTAGENESIS

JF - MUTAGENESIS

SN - 0267-8357

IS - 2

ER -